The present invention relates to a device to be used at the inlet end of a reactor vessel in which one or more substances are retained on a separation medium from a liquid passing through the vessel. This kind of separation can be carried out in batch-wise mode or in chromatography mode. The separation medium is typically in form of porous or non-porous particles that may be present as a packed or fluidised bed, the latter encompassing fully disordered fluidised beds (batch-wise mode) or classified or stabilised fluidised beds (chromatography fluidised mode).
The xe2x80x9cterm retained on a separation mediumxe2x80x9d means that the substance(s) are capable of interacting with the separation medium, such as in separations based on (a) affinity adsorption including ion exchange and other kinds of non-covalent bindings, (b) covalent binding and/or (c) on size exclusion.
Various devices to be used at the inlet side of this kind of reactors have been described in the background art. See for instance WO 9218237 (Amersham Pharmacia Biotech AB) and WO 0025883 (application no PCT/SE99/01957, Amersham Pharmacia Biotech AB), both of which are incorporated by reference.
Typically inlet devices have comprised
(a) distributor means which comprises a block or a plate and permits a liquid flow to pass through into the interior of the reactor vessel,
(b) an inlet block or plate having one or more through-going conduits permitting liquid to pass through the inlet block or plate,
(c) a distribution chamber defined by a space between the distributor means and the inlet block or plate, and
(d) a gross flow direction passing from the distributor chamber to and through the reactor vessel.
A recess in the inlet block typically defines the distribution chamber. The distribution block covers the recess. If the recess is tapered there may be no distinct walls of the chamber. If chamber has walls they are in the context of the invention included in the outlet side of the inlet block or plate, if not otherwise specified.
There has been a recent suggestion in the field to equip the outlet of the inlet conduits in the inlet block with xe2x80x9csprinkler meansxe2x80x9d (nozzles) (WO 0025883, FIG. 4, pages 16-17). The main purpose of the design has been to facilitate an even distribution of liquid to the distributor block. There is a suggestion that this design possibly will assist in keeping the chamber clean from sticky components.
The design with sprinkler means is illustrated in FIG. 1 of the present specification. There is a distribution chamber (1) having one or more conduits (2a,2b . . . ) projecting and permitting liquid flow through an inlet block (3) into the chamber (1). The chamber (1) is via distribution means (4) in liquid communication with the interior (5a) of a reactor vessel (5b) in which a separation medium is present. The distributor means may comprise a net/mesh (6) and/or a block (distributor block, 7) having open through passing channels permitting liquid flow between the chamber (1) and the interior of the reactor vessel (5). On the chamber end of each incoming conduit (2a,2b . . . ) there are sprinkler means (nozzles) (8) in form of a cap and openings (9) placed circularly in the wall of the end of the conduit just before the cap. The conduits (2a,2b . . . ) extend from the inlet block (3) from the inlet side (10) to the outlet side (11) (=inlet side/surface of the distribution chamber). The incoming liquid is in the variant shown distributed radially in a plane perpendicular to the flow direction in the conduit concerned, i.e. perpendicular to the central axis (12) of the chamber.
To each of the conduits (2a,2b . . . ) there are connected a tubing (31a,31b) that comes from a common tubing (37) equipped with a pump (38). Between the outlet end (11) and the nozzle (8) the conduit has a central tubular part in form of a central channel (32). At the outlet end of the reactor vessel (5) there is an outlet tubing (35) and an outlet adapter comprising a collector block (33), a collector chamber (34), an end block (36) with an outlet opening (39).
The inlet devices discussed above may be present as a bottom adapter or as a top adapter if the flow through the reactor vessel is upward or downward, respectively. If the flow direction is upward the outlet side (11) becomes the bottom/bottom surface of the distribution chamber.
The outlet side (11) is typically also the inlet side of the distribution chamber (1).
For reasons of simplicity the term xe2x80x9cblockxe2x80x9d in the instant specification contemplates true block dimensions and plate dimensions, if not otherwise specified.
In WO 91 00799 (Upfront Chromatography) there is described certain inlet devices that create a turbulent zone at the inlet end of the reactor vessel and a non-turbulent zone remote from the inlet end. The length of the turbulent zone is dependent on the flow velocity. The turbulent zone is created by the presence of agitating means (for instance a stirrer) in the inlet end of the reactor vessel. In many of the variants described in this publication the use of a distributor block becomes redundant. Liquids may enter through a side-wall of the reactor vessel/distributor.
Problems Associated with Back-ground Techniques
The liquid containing the substance to be adsorbed often contains particulate matters that have a tendency to sediment due to inappropriate flow conditions in various parts of a separation system, such as in inlet devices. Once sedimented, particulate material may start adhering to surfaces due to an inherent stickiness. This is particularly true for biologically derived liquids containing for instance cells, cell debris and/or other sticky particulates and/or sticky solutes. This problem has been found to be most severe for liquids deriving from cell culture broths and/or containing mammalian cells and/or mammalian cell debris. In inlet devices, for instance according to WO 0025883, it has turned out that particles of the separation media may assemble in the distribution chamber even if there is a check valve in the distributor block. Consequently the inlet devices described above are in need to be improved. The present invention has as its major objective to provide solutions to this kind of problems.
Accordingly a first objective of the invention is to provide an improved inlet device that at least partially circumvent the problems just discussed.
A second alternative is to provide an improved method in which these problems are reduced.
A third objective is a method for reducing the same problems.